ABSTRACT: STANDARD OF CARE CMT1, CMT2 and CMT4 are caused by mutations in > 80 genes. Despite the genetic heterogeneity there are clinical similarities in most patients, even if the speed of progression may vary. Distal wasting, weakness and sensory loss that begin in the lower limbs and progress proximally in a length-dependent manner characterize most forms of CMT. Despite progress in identifying its causes there are still no published comprehensive standards of care (SOC) for CMT. We have a unique opportunity to develop them. During the initial cycle of our RDCRC, we have enrolled over 6500 patients into the protocols of the INC. We have performed preliminary studies on the usage of next generation sequencing (NGS), the benefits of aerobic exercise and the approaches to orthopedic surgery in patients with CMT. All three of these areas are important to patients with CMT and all three lack SOC. In the upcoming cycle we propose the following three Specific Aims: Aim 1: Develop genetic diagnostic guidelines for CMT based on NGS technology. Aim 2: Develop evidence-based guidelines for the use of aerobic exercise in CMT. Aim 3: Convene an international workshop to develop SOC for CMT and to identify areas of SOC that need further study to develop evidence based guidelines.